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Luteolin is a flavonoid that occurs naturally in various fruits and vegetables. It has been shown that this compound possesses anti-inflammatory and antioxidant properties, which can significantly inhibit pathogenesis. A substantial amount of research has been performed to execute this compound’s role as an anticancer agent. Moreover, luteolin has the ability to block cell proliferation, inflammation, angiogenesis, and other cell signaling molecules that can contribute to cancer growth. This review aims to shed light on the efforts to present potential targets for luteolin in different cancers. Moreover, this review also explores the synergistic potential of this compound with other anticancer drugs. Despite its promising health-promoting benefits, it is essential to note that further research is needed based on safety, mechanism of action, efficacy, and clinical trials to reconnoiter its potential benefits in cancer management.

Tuberculosis (TB) is a serious disease that affects people worldwide, including in Saudi Arabia. The study analyzed the frequency of diagnosed TB cases, age-specific incidence rate, year of diagnosis, and prevalence of TB in Saudi Arabia from 2014 to 2020. Based on the National Tuberculosis Program (NTP) data, 21,120 patients were diagnosed with TB. The mean incidence rate of pulmonary TB and extra-pulmonary TB was approximately 6.92 and 2.33 per 100,000 population, respectively. The highest age-specific incidence rate was observed in the 25–35 year age group. The non-Saudi population (11,086 cases; 52.50%) was significantly more affected by both types of TB compared to the Saudi population (10,034 cases; 47.50%). The male population of Saudi and non-Saudi was significantly more affected by both types of TB. The highest overall mean incidence rate per 100,000 population was observed in the Jeddah and Jazan regions. The study's findings may have implications for supporting public health interventions and implementing a more effective TB control strategy program in Saudi Arabia. It suggests that immigrants from TB-endemic countries and religious visitors from high-risk countries should undergo pre and post-arrival screening for TB to reduce its incidence.

The escalation of environmental pathogenic microorganisms and disregard of public hygiene practices have resulted in the emergence of various skin infections within communities. Recent investigations have proposed that diverse snail mucus compositions may possess antimicrobial properties. Therefore, it is imperative to conduct further research to elucidate specific antibacterial characteristics inherent in the mucus of White Garden snail (Theba pisana). This study aimed to evaluate antibacterial activity of Theba pisana mucus extract against selected ATCC bacterial strains being Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, and MRSA. The assessment involved comparing antimicrobial activity of the mucus extract to various broad-spectrum antibiotics. The susceptibility of bacterial isolates to snail mucus secretions was assessed using agar well diffusion method on Muller Hilton Agar plates. After incubation at 37°C for 24 hours, various concentrations of snail slime including 100%, 75%, 50%, and 25% were applied. The findings reported that E. faecalis exhibited highest activity, with zone of inhibition measuring 24 mm, followed by K. pneumonia and S. aureus (16 mm), MRSA (14 mm), and E. coli (12 mm). However, at concentration of 25%, mucus extract exhibited effect only against E. faecalis. Moreover, the antimicrobial activity of several tested antibiotics demonstrated similarity to that of the mucus extract. Therefore, it revealed that secretions of T. pisana mucus may possess the potential to act as a source of antibacterial agents. This may become as an alternative agent to costly synthetic antibacterial compounds. However, further studies are required to exploit the mucus secretion in addressing the issue of antibiotic resistance.

Healthcare-associated infections pose a significant global health challenge, negatively impacting patient outcomes and burdening healthcare systems. A major contributing factor to healthcare-associated infections is the formation of biofilms, structured microbial communities encased in a self-produced extracellular polymeric substance matrix. Biofilms are critical in disease etiology and antibiotic resistance, complicating treatment and infection control efforts. Their inherent resistance mechanisms enable them to withstand antibiotic therapies, leading to recurrent infections and increased morbidity. This review explores the development of biofilms and their dual roles in health and disease. It highlights the structural and protective functions of the EPS matrix, which shields microbial populations from immune responses and antimicrobial agents. Key molecular mechanisms of biofilm resistance, including restricted antibiotic penetration, persister cell dormancy, and genetic adaptations, are identified as significant barriers to effective management. Biofilms are implicated in various clinical contexts, including chronic wounds, medical device-associated infections, oral health complications, and surgical site infections. Their prevalence in hospital environments exacerbates infection control challenges and underscores the urgent need for innovative preventive and therapeutic strategies. This review evaluates cutting-edge approaches such as DNase-mediated biofilm disruption, RNAIII-inhibiting peptides, DNABII proteins, bacteriophage therapies, antimicrobial peptides, nanoparticle-based solutions, antimicrobial coatings, and antimicrobial lock therapies. It also examines critical challenges associated with biofilm-related healthcare-associated infections, including diagnostic difficulties, disinfectant resistance, and economic implications. This review emphasizes the need for a multidisciplinary approach and underscores the importance of understanding biofilm dynamics, their role in disease pathogenesis, and the advancements in therapeutic strategies to combat biofilm-associated infections effectively in clinical settings. These insights aim to enhance treatment outcomes and reduce the burden of biofilm-related diseases.

The rise in antibiotic-resistant Staphylococcal infections necessitates innovative approaches to identify new therapeutic agents. This study investigates the application of machine learning models to identify potential phytochemical inhibitors against BacA, a target related to Staphylococcal infections. Active compounds were retrieved from BindingDB while the decoy was generated from DUDE. The RDKit was utilized for feature engineering. Machine learning models such as k-nearest neighbors (KNN), the support vector machine (SVM), random forest (RF), and naive Bayes (NB) were trained on an initial dataset consisting of 226 active chemicals and 2550 inert compounds. Accompanied by an MCC of 0.93 and an accuracy of 96%, the RF performed better. Utilizing the RF model, a library of 9000 phytochemicals was screened, identifying 300 potentially active compounds, of which 192 exhibited drug-like properties and were further analyzed through molecular docking studies. Molecular docking results identified Ergotamine, Withanolide E, and DOPPA as top inhibitors of the BacA protein, accompanied by interaction affinities of −8.8, −8.1, and −7.9 kcal/mol, respectively. Molecular dynamics (MD) was applied for 100 ns to these top hits to evaluate their stability and dynamic behavior. RMSD, RMSF, SASA, and Rg analyses showed that all complexes remained stable throughout the simulation period. Binding energy calculations using MMGBSA analysis revealed that the BacA_Withanolide E complex exhibited the most favorable binding energy profile with significant van der Waals interactions and a substantial reduction in gas-phase energy. It also revealed that van der Waals interactions contributed significantly to the binding stability of Withanolide E, while electrostatic interactions played a secondary role. The integration of machine learning models with molecular docking and MD simulations proved effective in identifying promising phytochemical inhibitors, with Withanolide E emerging as a potent candidate. These findings provide a pathway for developing new antibacterial agents against Staphylococcal infections, pending further experimental validation and optimization.

The worldwide prevalence of Diabetes Mellitus (DM) associated with Hepatitis C Virus (HCV) infection are reported with higher rates of morbidity and mortality. The frequency of HCV is approximately 3-4 million cases each year and in parallel the incidence of DM is increasing alarmingly. World Health Organization (WHO) has specified that DM will be the 7th leading cause of mortality by 2030. The increasing association between HCV and DM has been indicated by some significant reports recently. HCV infection leads to hepatic steatosis and rapid insulin resistance, which in turn upsurges the risk factors for hepatic fibrosis and hepatocellular carcinoma. This study is designed to examine the association between HCV and DM, and different risk factors associated with HCV infection in Qassim region, Kingdom of Saudi Arabia (KSA). A total of 634 blood samples were obtained from diabetic and non-diabetic patients. These blood samples were first screened for HCV infection by enzyme-linked immunosorbent assay (ELISA) and positive samples were again confirmed by TaqMan HCV quantitative test and the viral load in different samples was estimated. The HCV prevalence was identified as 2.5% in diabetic patients with a positive association between HCV and DM (RR= 1.24, OR= 1.77) which is not significant statistically. However, the HCV prevalence among diabetic females was significantly different from males (p

Silver nanoparticles (AgNPs) are leading the way in nanotechnological innovation, combining the captivating properties of silver with the accuracy of nanoscale engineering, thus revolutionizing material science. Three main techniques arise within the alchemical domains of AgNP genesis: chemical, physical, and biological synthesis. Each possesses its distinct form of magic for controlling size, shape, and scalability—key factors necessary for achieving expertise in the practical application of nanoparticles. The story unravels, describing the careful coordination of chemical reduction, the environmentally sensitive charm of green synthesis utilizing plant extracts, and the precise accuracy of physical techniques. AgNPs are highly praised in the field of healthcare for their powerful antibacterial characteristics. These little warriors display a wide-ranging attack against bacteria, fungi, parasites, and viruses. Their critical significance in combating hospital-acquired and surgical site infections is highly praised, serving as a beacon of hope in the fight against the challenging problem of antibiotic resistance. In addition to their ability to kill bacteria, AgNPs are also known to promote tissue regeneration and facilitate wound healing. The field of cancer has also observed the adaptability of AgNPs. The review documents their role as innovative carriers of drugs, specifically designed to target cancer cells with accuracy, minimizing harm to healthy tissues. Additionally, it explores their potential as cancer therapy or anticancer agents capable of disrupting the growth of tumors. In the food business, AgNPs are utilized to enhance the durability of packing materials and coatings by infusing them with their bactericidal properties. This results in improved food safety measures and a significant increase in the duration that products can be stored, thereby tackling the crucial issue of food preservation. This academic analysis recognizes the many difficulties that come with the creation and incorporation of AgNPs. This statement pertains to the evaluation of environmental factors and the effort to enhance synthetic processes. The review predicts future academic pursuits, envisioning progress that will enhance the usefulness of AgNPs and increase their importance from being new to becoming essential within the realms of science and industry. Besides, AgNPs are not only a subject of scholarly interest but also a crucial component in the continuous effort to tackle some of the most urgent health and conservation concerns of contemporary society. This review aims to explore the complex process of AgNP synthesis and highlight their numerous uses, with a special focus on their growing importance in the healthcare and food business sectors. This review invites the scientific community to explore the extensive possibilities of AgNPs in order to fully understand and utilize their potential.

Apigenin is a powerful flavone compound found in numerous fruits and vegetables, and it offers numerous health-promoting benefits. Many studies have evidenced that this compound has a potential role as an anti-inflammatory and antioxidant compound, making it a promising candidate for reducing the risk of pathogenesis. It has also been found to positively affect various systems in the body, such as the respiratory, digestive, immune, and reproductive systems. Apigenin is effective in treating liver, lung, heart, kidney, neurological diseases, diabetes, and maintaining good oral and skin health. Multiple studies have reported that this compound is capable of suppressing various types of cancer through the induction of apoptosis and cell-cycle arrest, suppressing cell migration and invasion, reduction of inflammation, and inhibiting angiogenesis. When used in combination with other drugs, apigenin increases their efficacy, reduces the risk of side effects, and improves the response to chemotherapy. This review broadly analyzes apigenin’s potential in disease management by modulating various biological activities. In addition, this review also described apigenin’s interaction with other compounds or drugs and the potential role of nanoformulation in different pathogeneses. Further extensive research is needed to explore the mechanism of action, safety, and efficacy of this compound in disease prevention and treatment.

Natural products and their bioactive compounds have been used for centuries to prevent and treat numerous diseases. Kaempferol, a flavonoid found in vegetables, fruits, and spices, is recognized for its various beneficial properties, including its antioxidant and anti-inflammatory potential. This molecule has been identified as a potential means of managing different pathogenesis due to its capability to manage various biological activities. Moreover, this compound has a wide range of health-promoting benefits, such as cardioprotective, neuroprotective, hepatoprotective, and anti-diabetic, and has a role in maintaining eye, skin, and respiratory system health. Furthermore, it can also inhibit tumor growth and modulate various cell-signaling pathways. In vivo and in vitro studies have demonstrated that this compound has been shown to increase efficacy when combined with other natural products or drugs. In addition, kaempferol-based nano-formulations are more effective than kaempferol treatment alone. This review aims to provide detailed information about the sources of this compound, its bioavailability, and its role in various pathogenesis. Although there is promising evidence for its ability to manage diseases, it is crucial to conduct further investigations to know its toxicity, safety aspects, and mechanism of action in health management.

Abstract Clustered regularly interspaced short palindromic repeats‐associated protein (CRISPR/Cas9), an adaptive microbial immune system, has been exploited as a robust, accurate, efficient and programmable method for genome targeting and editing. This innovative and revolutionary technique can play a significant role in animal modeling, in vivo genome therapy, engineered cell therapy, cancer diagnosis and treatment. The CRISPR/Cas9 endonuclease system targets a specific genomic locus by single guide RNA (sgRNA), forming a heteroduplex with target DNA. The Streptococcus pyogenes Cas9/sgRNA:DNA complex reveals a bilobed architecture with target recognition and nuclease lobes. CRISPR/Cas9 assembly can be hijacked, and its nanoformulation can be engineered as a delivery system for different clinical utilizations. However, the efficient and safe delivery of the CRISPR/Cas9 system to target tissues and cancer cells is very challenging, limiting its clinical utilization. Viral delivery strategies of this system may have many advantages, but disadvantages such as immune system stimulation, tumor promotion risk and small insertion size outweigh these advantages. Thus, there is a desperate need to develop an efficient non‐viral physical delivery system based on simple nanoformulations. The delivery strategies of CRISPR/Cas9 by a nanoparticle‐based system have shown tremendous potential, such as easy and large‐scale production, combination therapy, large insertion size and efficient in vivo applications. This review aims to provide in‐depth updates on Streptococcus pyogenic CRISPR/Cas9 structure and its mechanistic understanding. In addition, the advances in its nanoformulation‐based delivery systems, including lipid‐based, polymeric structures and rigid NPs coupled to special ligands such as aptamers, TAT peptides and cell‐penetrating peptides, are discussed. Furthermore, the clinical applications in different cancers, clinical trials and future prospects of CRISPR/Cas9 delivery and genome targeting are also discussed.

Pro-inflammatory macrophage polarization is crucial in acute inflammatory diseases like Acute lung injury (ALI), and acute respiratory distress syndrome (ARDS). Prostaglandin E2 (PGE2) is believed to promote inflammation in such cases. Therefore, our study aimed to deliver anti-prostaglandin E synthase 2 small interfering RNA antibodies (anti-PGE2-siRNA) through lipid nanoparticles (LNPs) in RAW264.7 (The murine macrophage cell line) to find a possible cure to the acute inflammatory diseases. LNPs were synthesized by using thin layer evaporation method and were characterized by dynamic light scattering (DLS), Zeta potential, SEM and TEM analysis. The obtained NPs were spherical with an average size of 73 nm and zeta potential +29mV. MTT assay revealed that these NPs were non-toxic in nature. Gel retardation assay displayed 5:2 ratio of siRNA and NPs as the best siRNA:LNPs ratio for the delivery of siRNA into cells. After siRNA delivery by using LNPs, real time gene expression analysis revealed significant decrease in the expression of PGE2. Western blot results confirmed that silencing of PGE2 gene influence inducible nitric oxide synthase (iNOS) and interlukin-1β (1L-1β), markers involved in pro-inflammatory macrophage polarization. Our study revealed that LNPs synthesized in present study can be one of the effective methods to deliver anti-PGE2-siRNA to control pro-inflammatory macrophage polarization for the treatment of acute inflammatory response.

(1) Background: SARS-CoV-2 Omicron BA.1 is the most common variation found in most countries and is responsible for 99% of cases in the United States. To overcome this challenge, there is an urgent need to discover effective inhibitors to prevent the emerging BA.1 variant. Natural products, particularly flavonoids, have had widespread success in reducing COVID-19 prevalence. (2) Methods: In the ongoing study, fifteen compounds were annotated from Echium angustifolium and peach (Prunus persica), which were computationally analyzed using various in silico techniques. Molecular docking calculations were performed for the identified phytochemicals to investigate their efficacy. Molecular dynamics (MD) simulations over 200 ns followed by molecular mechanics Poisson–Boltzmann surface area calculations (MM/PBSA) were performed to estimate the binding energy. Bioactivity was also calculated for the best components in terms of drug likeness and drug score. (3) Results: The data obtained from the molecular docking study demonstrated that five compounds exhibited remarkable potency, with docking scores greater than −9.0 kcal/mol. Among them, compounds 1, 2 and 4 showed higher stability within the active site of Omicron BA.1, with ΔGbinding values of −49.02, −48.07, and −67.47 KJ/mol, respectively. These findings imply that the discovered phytoconstituents are promising in the search for anti-Omicron BA.1 drugs and should be investigated in future in vitro and in vivo research.

Biofilms, which consist of microorganisms enclosed in an extracellular polymeric material (EPS), hold immense importance in the fields of environmental research, industry, and medicine. They play a significant role in ecosystem dynamics and stability, but they also pose issues such as biofouling, corrosion, and pollution. Biofilms in medical environments are linked to persistent infections and elevated healthcare expenses. The EPS matrix plays a crucial role in maintaining the structural integrity and antibiotic resistance of these structures. The research primarily investigates the role of the EPS matrix in facilitating horizontal gene transfer among biofilm communities, with a particular emphasis on EPS and its impact on this process. The process is recognized as a pivotal mechanism in the emergence of antibiotic resistance, underscoring the crucial function of EPS in the dynamics of biofilms. The analysis also highlights the significant financial constraints caused by biofilms in several industries. Biofilm-associated infections in the healthcare sector result in escalated treatment expenses and extended hospitalization periods. In an industrial context, biofilms have a role in increasing maintenance expenses and product contamination, emphasizing the need for efficient management solutions. This review presents the most recent progress in biofilm research, emphasizing the utilization of sophisticated imaging tools and molecular methodologies. In addition to conventional imaging techniques, the research explores the utilization of sophisticated molecular tools, such as DNA and RNA sequencing, in conjunction with proteomics. These approaches are essential for assessing the genetic and metabolic mechanisms that regulate biofilm development and antibiotic resistance. The review underscores the significance of employing an interdisciplinary methodology in the study of biofilms. By incorporating a range of approaches, such as sophisticated imaging and molecular analysis, a comprehensive understanding of biofilm dynamics may be achieved. This approach also opens up possibilities for developing novel solutions to address the negative impacts of biofilms on health, industry, and the environment.

Luteolin, a flavonoid, is mainly found in various vegetables and fruits, including carrots, cabbages, onions, parsley, apples, broccoli, and peppers. Extensive research in vivo and in vitro has been performed to explore its role in disease prevention and treatment. Moreover, this compound possesses the ability to combat cancer by modulating cell-signaling pathways across various types of cancer. The studies have confirmed that luteolin can inhibit cancer-cell survival and proliferation, angiogenesis, invasion, metastasis, mTOR/PI3K/Akt, STAT3, Wnt/β-catenin, and cell-cycle arrest, and induce apoptosis. Further, scientific evidence describes that this compound plays a vital role in the up/down-regulation of microRNAs (miRNAs) in cancer therapy. This review aims to outline the anti-cancer mechanisms of this compound and its molecular targets. However, a knowledge gap remains regarding the studies on its safety and efficacy and clinical trials. Therefore, it is essential to conduct more research based on safety, efficacy, and clinical trials to explore the beneficial role of this compound in disease management, including cancer.

Abstract The Rift Valley fever virus (RVFV) is a zoonotic arbovirus and pathogenic to both humans and animals. Currently, no proven effective RVFV drugs or licensed vaccine are available for human or animal use. Hence, there is an urgent need to develop effective treatment options to control this viral infection. RVFV glycoprotein N (GN), glycoprotein C (GC), and nucleocapsid (N) proteins are attractive antiviral drug targets due to their critical roles in RVFV replication. In present study, an integrated docking-based virtual screening of more than 6000 phytochemicals with known antiviral activities against these conserved RVFV proteins was conducted. The top five hit compounds, calyxin C, calyxin D, calyxin J, gericudranins A, and blepharocalyxin C displayed optimal binding against all three target proteins. Moreover, multiple parameters from the molecular dynamics (MD) simulations and MM/GBSA analysis confirmed the stability of protein–ligand complexes and revealed that these compounds may act as potential pan-inhibitors of RVFV replication. Our computational analyses may contribute toward the development of promising effective drugs against RVFV infection.

Cancer is a major public health concern worldwide in terms of mortality. The exact reason behind the development of cancer is not understood clearly, but it is evidenced that alcohol consumption, radiation, and exposure to chemicals are main players in this pathogenesis. The current mode of treatments such as surgery, chemotherapy, and radiotherapy are effective, but, still, cancer is a major problem leading to death and other side effects. However, safer and effective treatment modules are needed to overcome the adverse effects of current treatment modules. In this regard, natural compounds have been recognized to ameliorate diseases by exerting anti-inflammatory, anti-oxidative, and anti-tumor potential through several mechanisms. Mangiferin, a xanthone C-glucoside, is found in several plant species including Mangifera indica (mango), and its role in disease prevention has been confirmed through its antioxidant and anti-inflammatory properties. Furthermore, its anti-cancer-potential mechanism has been designated through modulation of cell signaling pathways such as inflammation, angiogenesis, PI3K/AKT, apoptosis, and cell cycle. This article extensively reviews the anticancer potential of mangiferin in different cancers through the modulation of cell signaling pathways. Moreover, the synergistic effects of this compound with some commonly used anti-cancer drugs against different cancer cells are discussed. More clinical trials should be performed to reconnoiter the anti-cancer potential of this compound in human cancer treatment. Further, understanding of mechanisms of action and the safety level of this compound can help to manage diseases, including cancer.

Objectives: Here, we prepared a liposome-based vaccine formulation containing Middle East Respiratory Syndrome Coronavirus papain-like protease (MERS-CoV-PLpro). Methods: A persistent leukopenic condition was induced in mice by injecting cyclophosphamide (CYP) three days before each dose of immunization. Mice were immunized on days 0, 14 and 21 with α-GalCer-bearing MERS-CoV PLpro-encapsulated DPPC-liposomes (α-GalCer-MERS-PLpro-liposomes or MERS-CoV PLpo-encapsulated DPPC-liposomes (MERS-PLpro-liposomes), whereas the antigen emulsified in Alum (MERS-PLpro-Alum) was taken as a control. On day 26, the blood was taken from the immunized mice to analyze IgG titer, whereas the splenocytes were used to analyze the lymphocyte proliferation and the level of cytokines. In order to assess the memory immune response, mice were given a booster dose after 150 days of the last immunization. Results: The higher levels of MERS-CoV-PLpro-specific antibody titer, IgG2a and lymphocyte proliferation were noticed in mice immunized with α-GalCer-MERS-PLpro-liposomes. Besides, the splenocytes from mice immunized with α-GalCer-MERS-PLpro-liposomes produced larger amounts of IFN-γ as compared to the splenocytes from MERS-PLpro-liposomes or MERS- PLpro-Alum immunized mice. Importantly, an efficient antigen-specific memory immune response was observed in α-GalCer-MERS-PLpro-liposomes immunized mice. Conclusions: These findings suggest that α-GalCer-MERS-PLpro-liposomes may substantiate to be a successful vaccine formulation against MERS-CoV infection, particularly in immunocompromised individuals.

To investigate the biosynthesis of silver nanoparticles (T-AgNPs) using leaf extract of Tamarix articulata and their possible role in attenuation of oxidative stress mediated human diseases. T-AgNPs were characterized by several biophysical techniques. Various health beneficial activities were also investigated. The synthesized T-AgNPs showed an absorption peak at 413 nm on UV-Visible spectroscopy indicating the surface plasmon resonance of the nanoparticles. TEM analysis clearly showed that particles were spherical with an average size of about 25 nm. SEM image analysis confirmed the spherical shape of T-AgNPs. T-AgNPs (600 µg/ml) showed effective DPPH scavenging (68.23%), ferric reducing (68.23%), and hydrogen peroxide reducing (70.09%) activities. Besides, T-AgNPs at 600 µg/ml, also showed strong anti-glycating, and AGEs formation inhibitory activities as indicated by reduced browning intensity (51.62%), aggregation index (48.86%), and cross amyloid structures (53.62%) as compared to positive controls (100%). A 600 µg/ml of T-AgNPs was found to have potent in vitro anti-inflammatory activity as revealed by albumin denaturation inhibition (73.19%), protease activity inhibition (70.196%), membrane stability against heat (74.16%), and hyposaline (72.98%) induced hemolysis as compared to controls. Altogether, these findings confirm that T-AgNPs can be promising candidates for the development of antioxidant, anti-inflammatory, membrane stabilizing, antiglycating and AGEs inhibitory agents.

Door handles are being reported to harbor a diverse group of microorganisms, mainly bacteria. Presence of pathogenic and antibiotic-resistant bacteria in the door handles carry risk to the health of the public. For this reason, a study was carried in the Qassim region of Saudi Arabia by isolating bacteria from the pharmacy door handles from four different areas. Total 100 samples were collected by wiping the door handles with a sterile cotton swab soaked in sterile water. Microorganisms were isolated using Blood agar and MacConkey agar and identified following standard microbiological procedure. Siemens MicroScan Walkaway system was used for determination of antibiotic susceptibility pattern. In total, 301 bacteria from 13 bacterial species were isolated and identified. The predominant bacterial species include Staphylococcus spp. 56.48% followed by Bacillus spp. 12.29% and Micrococcus spp. 10.30%. Gram-negative bacteria like Shigella sonnei and Salmonella paratyphiA were also isolated. Being the most predominant species, Antibiotic resistance pattern of 39 Staphylococcus spp. were determined. 38.46% of the Staphylococcus spp. were found to be resistant to Cefoxitin, and 30.76% were beta-lactamase producing. The results also indicated that about one -third of Staphylococcus spp. were methicillin resistant. The door handles of pharmacies in the Qassim region carry risk to the health of the public. Proper hygienic measures are recommended for the public health safety until doors are made automatic and touch-free.

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that originated in Chinese city of Wuhan has caused around 906,092 deaths and 28,040,853 confirmed cases worldwide (https://covid19.who.int/, 11 September 2020). In a life-threatening situation, where there is no specific and licensed anti-COVID-19 vaccine or medicine available; the repurposed drug might act as a silver bullet. Currently, more than 211 vaccines, 80 antibodies, 31 antiviral drugs, 35 cell-based, 6 RNA-based and 131 other drugs are in clinical trials. It is therefore utter need of the hour to develop an effective drug that can be used for the treatment of COVID-19 before a vaccine can be developed. One of the best-characterized and attractive drug targets among coronaviruses is the main protease (3CLpro). Therefore, the current study focuses on the molecular docking analysis of TAT-peptide47–57 (GRKKRRQRRRP)-conjugated repurposed drugs (i.e., lopinavir, ritonavir, favipiravir, and hydroxychloroquine) with SARS-CoV-2 main protease (3CLpro) to discover potential efficacy of TAT-peptide (TP) - conjugated repurposing drugs against SARS-CoV-2. The molecular docking results validated that TP-conjugated ritonavir, lopinavir, favipiravir, and hydroxychloroquine have superior and significantly enhanced interactions with the target SARS-CoV-2 main protease. In-silico approach employed in this study suggests that the combination of the drug with TP is an excelling alternative to develop a novel drug for the treatment of SARS-CoV-2 infected patients. The development of TP based delivery of repurposing drugs might be an excellent approach to enhance the efficacy of the existing drugs for the treatment of COVID-19. The predictions from the results obtained provide invaluable information that can be utilized for the choice of candidate drugs for in vitro, in vivo and clinical trials. The outcome from this work prove crucial for exploring and developing novel cost-effective and biocompatible TP conjugated anti-SARS-CoV-2 therapeutic agents in immediate future.

Green nanomaterials have gained much attention due to their potential use as therapeutic agents. The present study investigated the production of silver nanoparticles (AgNPs) from a silver-resistant Bacillus safensis TEN12 strain, which was isolated from metal contaminated soil and taxonomically identified through 16S rRNA gene sequencing. The formation of AgNPs in bacterial culture was confirmed by using UV–vis spectroscopy with an absorption peak at 426.18 nm. Fourier transform infrared (FTIR) spectroscopy confirmed the involvement of capping proteins and alcohols for stabilization of AgNPs. Moreover, X-ray diffraction analysis (XRD), scanning and transmission electron microscopy (SEM and TEM) confirmed the crystalline nature and spherical shape of AgNPs with particle size ranging from 22.77 to 45.98 nm. The energy dispersive X-ray spectroscopy (EDX) revealed that 93.54% silver content is present in the nano-powder. AgNPs showed maximum antibacterial activity (20.35 mm and 19.69 mm inhibition zones) at 20 µg mL−1 concentration against Staphylococcus aureus and Escherichia coli, respectively and significantly reduced the pathogen density in broth culture. Furthermore, AgNPs demonstrated significant anticancer effects in the human liver cancer cell line (HepG2) in MTT assay, whereas, no cytotoxic effects were demonstrated by AgNPs on normal cell line (HEK293). The present study suggests that the biogenic AgNPs may substitute chemically synthesized drugs with wider applications as antibacterial and anticancer agents.

In the present study, Indole-based-oxadiazole (1A-17A) compounds were successfully synthesized. The structures of all synthesized compounds were fully characterized by different sophisticated spectroscopic techniques such 1H NMR, 13C NMR, and HREI-MS. Further, the synthesized compounds were explored to investigate their broad-spectrum antibacterial and antibiofilm potential against multidrug resistant Pseudomonas aeruginosa (MDR-PA) and methicillin resistant Staphylococcus aureus (MRSA). The compounds possessed a broad spectrum of antibacterial activity having MIC values of values 1–8 mg/ml against the tested microorganisms. Compound A6 and A7 shows maximum antibacterial activity against MDR-PA, whereas A6, A7 and A11 shows highest activity against MRSA. Furthermore, antibiofilm assay shows that A6, A7 and A11 showed maximum inhibition of biofilm formation and it was found that at 4 mg/ml; A6, A7 and A11 inhibit MRSA biofilm formation by 81.1, 77.5 and 75.9%, respectively; whereas in case of P. aeruginosa; A6 and A7 showed maximum biofilm inhibition and inhibit biofilm formation by 81.5 and 73.7%, respectively. Molecular docking study showed that compounds A6, A7, A8, A10, and A11 had high binding affinity to bacterial peptidoglycan, indicating their potential inhibitory activity against tested bacteria, whereas A6 and A11 were found to be the most effective inhibitors of SARS CoV-2 main protease (3CLpro), with a binding affinity of − 7.78 kcal/mol. Furthermore, SwissADME and pkCSM-pharmacokinetics online tools was applied to calculate the ADME/Tox profile of the synthesized compounds and the toxicity of these chemicals was found to be low. The Lipinski, Veber, Ghose, and Consensus LogP criteria were also used to predict drug-likeness levels of the compounds. Our findings imply that the synthesized compounds could be a useful for the preventing and treating biofilm-related microbial infection as well as SARS-CoV2 infections.

IntroductionEsophageal cancer ranks the sixth most diagnosed cancer worldwide, and the morality incidence of this disease is rapidly growing worldwide. A retrospective observational population-based epidemiological study of esophageal cancer has been conducted, and data are based on the cancer registry of the National Health Information Center Saudi from 2006 to 2016. This study described the age-standardized incidence rates (ASIRs) and crude incidence rates (CIRs) of esophageal cancer based on age groups, diagnosis year, and administrative areas in Saudi Arabia populations to examine its distributions and trends in Saudi Arabia.MethodFor the statistical assessment of data, sex ratio, t-test, the Kruskal–Wallis test, and descriptive statistics were performed using SPSS version 20.0 (IBM Corporation, Armonk, NY, USA). A total of 755 and 597 cases of esophageal cancer in men and women, respectively, were reported from 2006 to 2016 in Saudi Arabia.ResultsOut of all esophageal cases, the highest number of cases was observed in the age group

Emergence of multidrug resistant pathogens is increasing globally at an alarming rate with a need to discover novel and effective methods to cope infections due to these pathogens. Green nanoparticles have gained attention to be used as efficient therapeutic agents because of their safety and reliability. In the present study, we prepared zinc oxide nanoparticles (ZnO NPs) from aqueous leaf extract of Acacia arabica. The nanoparticles produced were characterized through UV-Visible spectroscopy, scanning electron microscopy, and X-ray diffraction. In vitro antibacterial susceptibility testing against foodborne pathogens was done by agar well diffusion, growth kinetics and broth microdilution assays. Effect of ZnO NPs on biofilm formation (both qualitatively and quantitatively) and exopolysaccharide (EPS) production was also determined. Antioxidant potential of green synthesized nanoparticles was detected by DPPH radical scavenging assay. The cytotoxicity studies of nanoparticles were also performed against HeLa cell lines. The results revealed that diameter of zones of inhibition against foodborne pathogens was found to be 16-30 nm, whereas the values of MIC and MBC ranged between 31.25-62.5 μg/ml. Growth kinetics revealed nanoparticles bactericidal potential after 3 hours incubation at 2 × MIC for E. coli while for S. aureus and S. enterica reached after 2 hours of incubation at 2 × MIC, 4 × MIC, and 8 × MIC. 32.5-71.0% inhibition was observed for biofilm formation. Almost 50.6-65.1% (wet weight) and 44.6-57.8% (dry weight) of EPS production was decreased after treatment with sub-inhibitory concentrations of nanoparticles. Radical scavenging potential of nanoparticles increased in a dose dependent manner and value ranged from 19.25 to 73.15%. Whereas cytotoxicity studies revealed non-toxic nature of nanoparticles at the concentrations tested. The present study suggests that green synthesized ZnO NPs can substitute chemical drugs against antibiotic resistant foodborne pathogens.

The current study aimed to investigate the antioxidant, anti-inflammatory and hepatoprotective activity of olive fruit pulp extract (OFPE) through in vivo- and in vitro-based studies. Oral administration of OFPE demonstrated a significant reduction in liver biomarker enzymes, inflammatory marker (IL-6, TNF-α, and C-reactive protein (CRP)) level and recovered the antioxidant enzymes and total antioxidant capacity levels when compared to CCl4 treated group. The histopathological alterations were seen in CCl4 treated mice. The hepatocyte architecture was maintained in OFPE treated group as compared to the CCl4 treated group. The anti-inflammatory activity of the OFPE was evaluated through in vitro and was found to be similar with a reference drug, ibuprofen. Current findings revealed that OFPE displays hepatoprotective effect through enhancement of antioxidant enzyme level, reduction of anti-inflammatory and maintenance of hepatocyte architecture. Thus, olive fruit extract might be utilized as a therapeutic alternative in the treatment of hepatic complications.

Cancer is a main culprit and the second-leading cause of death worldwide. The current mode of treatment strategies including surgery with chemotherapy and radiation therapy may be effective, but cancer is still considered a major cause of death. Plant-derived products or their purified bioactive compounds have confirmed health-promoting effects as well as cancer-preventive effects. Among these products, flavonoids belong to polyphenols, chiefly found in fruits, vegetables and in various seeds/flowers. It has been considered to be an effective antioxidant, anti-inflammatory and to play a vital role in diseases management. Besides these activities, flavonoids have been revealed to possess anticancer potential through the modulation of various cell signaling molecules. In this regard, fisetin, a naturally occurring flavonoid, has a confirmed role in disease management through antioxidant, neuro-protective, anti-diabetic, hepato-protective and reno-protective potential. As well, its cancer-preventive effects have been confirmed via modulating various cell signaling pathways including inflammation, apoptosis, angiogenesis, growth factor, transcription factor and other cell signaling pathways. This review presents an overview of the anti-cancer potential of fisetin in different types of cancer through the modulation of cell signaling pathways based on in vivo and in vitro studies. A synergistic effect with anticancer drugs and strategies to improve the bioavailability are described. More clinical trials need to be performed to explore the anti-cancer potential and mechanism-of-action of fisetin and its optimum therapeutic dose.

The roles of medicinal plants or their purified bioactive compounds have attracted attention in the field of health sciences due to their low toxicity and minimal side effects. Baicalein is an active polyphenolic compound, isolated from Scutellaria baicalensis, and plays a significant role in the management of different diseases. Epidemiologic studies have proven that there is an inverse association between baicalein consumption and disease severity. Baicalein is known to display anticancer activity through the inhibition of inflammation and cell proliferation. Additionally, the anticancer potential of baicalein is chiefly mediated through the modulation of various cell-signaling pathways, such as the induction of apoptosis, autophagy, cell cycle arrest, inhibition of angiogenesis, signal transducer and activator of transcription 3, and PI3K/Akt pathways, as well as the regulation of other molecular targets. Therefore, the current review aimed to explore the role of baicalein in different types of cancer along with mechanisms of action. Besides this, the synergistic effects with other anti-cancerous drugs and the nano-formulation based delivery of baicalein have also been discussed.

Cancer is the utmost common disease-causing death worldwide, characterized by uncontrollable cell division with the potential of metastasis. Overexpression of the Inhibitors of Apoptosis proteins (IAPs) and autophagy correlates with tumorigenesis, therapeutic resistance, and reoccurrence after anticancer therapies. This study illuminates the role and efficacy of smac mimetic compound BV6 alone and in co-treatment with death ligands such as TRAIL and TNFα in the regulation of cell death mechanisms, i.e., apoptosis and autophagy. In this study, MTT assays, wound healing assays, and cellular and nuclear morphological studies were done. DAPI staining, AO/EtBr staining and AnnexinV/PI FACS was done to study the apoptosis. The expression of IAPs and autophagy biomarkers was analyzed using Real time-PCR and western blotting. Meanwhile, TEM demonstrated autophagy and cellular autophagic vacuoles in response to the BV6. The result shows a promising anti-cancer effect of BV6 alone as well as in combinational treatment with TRAIL and TNFα, compared to the lone treatment of TRAIL and TNFα in both breast cancer cell lines. The smac mimetic compound might provide an alternative combinational therapy with conventional anticancer therapies to tackle their inefficiency at the advanced stage of cancer, cancer resistance, and reoccurrence. Also, IAPs and autophagic proteins could act as potent target molecules for the development of novel anti-cancer drugs in pathogenesis and the betterment of regimens for cancer.

The implants are increasingly being a part of modern medicine in various surgical procedures for functional or cosmetic purposes. The progressive use of implants is associated with increased infectious complications and prevention of such infections always remains precedence in the clinical settings. The preventive approaches include the systemic administration of antimicrobial agents before and after the surgical procedures as well as the local application of antibiotics. The relevant literature and existing clinical practices have highlighted the role of antimicrobial coating approaches in the prevention of implants associated infections, although the applications of these strategies are not yet standardized, and the clinical efficacy is not much clear. The adequate data from the randomized control trials is challenging because of the unavailability of a large sample size although it is compulsory in this context to assess the clinical efficacy of preemptive practices. This review compares the efficacy of preventive approaches and the prospects of antimicrobial-coated implants in preventing implant-related infections.

Nanoparticles (NPs) prepared through safer, eco-friendly and natural-based products can be used various applications including antimicrobial and biomedical applications. Quorum sensing (QS) is a complex system for intercellular communication that regulates the expression of many virulence determinants, in the opportunistic Pseudomonas aeruginosa. Thus, the disruption of QS-mediated communication system could be an alternative strategy to combat infection caused by drug resistant P. aeruginosa. In this study, zinc oxide nanoparticles (ZnO NPs) were synthesized by using seed extract of Butea monosperma and further characterized by XRD, SEM and TEM. The biosynthesized ZnO NPs were then subjected to the investigation of their antibacterial, antibiofilm activities as well as the anti-quorum sensing potentialities for biomedical applications. The minimum inhibitory concentration (MIC) value against P. aeruginosa was found 1600 µg/ml, and it was found that ZnO NPs effectively reduced virulence factors Viz. swarming and swimming of P. aeruginosa by 62.8 and 45%, respectively. Exopolysaccharides production was also affected by ZnO NPs which indicate the disruption of biofilm formation. Further, the in silico docking analysis displayed that ZnO NPs efficiently interacted within QS (Las/Rhl) mechanism of P. aeruginosa by binding to the catalytic cleft of LasI synthase (Gly-116-ZnO = 2.8 Å), RhlI synthase (Gly-180-ZnO = 3.7 Å) and transcription receptor protein LasR receptor (Asn-141-ZnO = 2.9 Å), RhlR receptor (Tyr-72-ZnO = 2.6 Å). Thus, it was concluded that the effective interaction of ZnO NPs with Las and Rhl system led to the inactivation of autoinducers such as N-acyl homoserine lactones (AHL) molecules which finally led to the inactivation of QS and down regulation of virulence determinants. Consequently, the present in vitro and in silico results obtained suggest that the synthesized ZnO NPs can be efficiently used as potent antimicrobial agents to prevent the colonization, biofilm formation as well as anti-QS-mediated determinants caused by pathogenic drug resistant bacteria.

Oxidative stress, hyper-inflammatory responses, and protein glycation are the chief contributing factors in the pathogenesis of several diseases. This study aimed to explore the therapeutic role of myrrh in health management through in vitro and in silico studies. Antioxidant potential, anti-inflammatory potential, antiglycation, and advanced glycation end products (AGEs) formation inhibition activities were determined by various in vitro assays. Molecular docking was performed to predict the non-covalent binding of macromolecules (receptor) and a small molecule (ligand). Myrrh extract contained significant antioxidant activity as reflected by FRAP value (16.12 µg ascorbic acid/100 mg dry weight), the maximum percentage of DPPH scavenging (57.71%), and maximum hydrogen peroxide reducing activity (58.71%) at a concentration of 600 µg/mL. Further, the extract exhibited maximum protection from bovine serum albumin (BSA) denaturation inhibition (53.47%), anti-proteinase action (43.517%), and egg albumin denaturation inhibition (44.95%) at a dose of 600 µg/mL concentration. Myrrh is used in pharmacy as an antiseptic, anti-inflammatory, antimicrobial, antifungal, and anti-venom remedy. This study aimed to explore the antioxidant, anti-inflammatory, antiarthritic, antiglycation, and advanced glycation end products (AGEs) formation inhibition ability of methanolic myrrh extract. It was found that myrrh has good antioxidant potential due to plenty of flavonoids and polyphenolic compounds, as reflected by results of the 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH) assay, FRAP (ferric reducing antioxidant power) test, and hydrogen peroxide reducing test. Furthermore, myrrh methanolic extract was found to be significantly effective against heat-induced albumin denaturation, and percent inhibition of denaturation increases with increased extract concentration. The presence of myrrh extract at a dose of 600 μg/mL decreased browning intensity (59.38%), percent aggregation index (59.88%), and percentage amyloid structure (56.13%). We used molecular docking tools to study the role of myrrh in oxidative stress (Catalase), antioxidant property (Superoxide dismutase), and antiviral property (spike protein S). The molecular docking analysis confirmed four phytoconstituents; 2,3-Furandione, Curzerene, delta-Elemene, and Furanoeudesma-1,3-Diene interact with catalase and superoxide dismutase. Curzerene and Furanoeudesma-1,3-Diene showed remarkable interaction with SARS-CoV-2 spike protein S. Our data suggest that myrrh resin extract can be used to develop a suitable alternative therapy for various diseases linked with oxidative stress, inflammation, glycation, and AGEs.

Cancer is the leading cause of death worldwide. In spite of advances in the treatment of cancer, currently used treatment modules including chemotherapy, hormone therapy, radiation therapy and targeted therapy causes adverse effects and kills the normal cells. Therefore, the goal of more effective and less side effects-based cancer treatment approaches is still at the primary position of present research. Medicinal plants or their bioactive ingredients act as dynamic sources of drugs due to their having less side effects and also shows the role in reduction of resistance against cancer therapy. Apigenin is an edible plant-derived flavonoid that has received significant scientific consideration for its health-promoting potential through modulation of inflammation, oxidative stress and various other biological activities. Moreover, the anti-cancer potential of apigenin is confirmed through its ability to modulate various cell signalling pathways, including tumor suppressor genes, angiogenesis, apoptosis, cell cycle, inflammation, apoptosis, PI3K/AKT, NF-κB, MAPK/ERK and STAT3 pathways. The current review mainly emphases the potential role of apigenin in different types of cancer through the modulation of various cell signaling pathways. Further studies based on clinical trials are needed to explore the role of apigenin in cancer management and explain the possible potential mechanisms of action in this vista.

Antimicrobial resistance has become a significant health issue because of the misuse of antibiotics in our daily lives, resulting in high rates of morbidity and mortality. Hafnia alvei is a rod-shaped, Gram-negative and facultative anaerobic bacteria. The medical community has emphasized H. alvei’s possible association with gastroenteritis. As of now, there is no licensed vaccine for H. alvei, and as such, computer aided vaccine design approaches could be an ideal approach to highlight the potential vaccine epitopes against this bacteria. By using bacterial pan-genome analysis (BPGA), we were able to study the entire proteomes of H. alvei with the aim of developing a vaccine. Based on the analysis, 20,370 proteins were identified as core proteins, which were further used in identifying potential vaccine targets based on several vaccine candidacy parameters. The prioritized vaccine targets against the bacteria are; type 1 fimbrial protein, flagellar hook length control protein (FliK), flagellar hook associated protein (FlgK), curli production assembly/transport protein (CsgF), fimbria/pilus outer membrane usher protein, fimbria/pilus outer membrane usher protein, molecular chaperone, flagellar filament capping protein (FliD), TonB-dependent hemoglobin /transferrin/lactoferrin family receptor, Porin (OmpA), flagellar basal body rod protein (FlgF) and flagellar hook-basal body complex protein (FliE). During the epitope prediction phase, different antigenic, immunogenic, non-Allergenic, and non-Toxic epitopes were predicted for the above-mentioned proteins. The selected epitopes were combined to generate a multi-epitope vaccine construct and a cholera toxin B subunit (adjuvant) was added to enhance the vaccine’s antigenicity. Downward analyses of vaccines were performed using a vaccine three-dimensional model. Docking studies have confirmed that the vaccine strongly binds with MHC-I, MHC-II, and TLR-4 immune cell receptors. Additionally, molecular dynamics simulations confirmed that the vaccine epitopes were exposed to nature and to the host immune system and interpreted strong intermolecular binding between the vaccine and receptors. Based on the results of the study, the model vaccine construct seems to have the capacity to produce protective immune responses in the host, making it an attractive candidate for further in vitro and in vivo studies.

Camel milk (CM) constitutes an important dietary source in the hot and arid regions of the world. CM is a colloidal mixture of nutritional components (proteins, carbohydrates, lipids, vitamins, and minerals) and non-nutritional components (hormones, growth factors, cytokines, immunoglobulins, and exosomes). Although the majority of previous research has been focused on the nutritional components of CM; there has been immense interest in the non-nutritional components in the recent past. Reckoning with these, in this review, we have provided a glimpse of the recent trends in CM research endeavors and attempted to provide our perspective on the therapeutic efficacy of the nutritional and non-nutritional components of CM. Interestingly, with concerted efforts from the research fraternities, convincing evidence for the better understanding of the claimed traditional health benefits of CM can be foreseen with great enthusiasm and is indeed eagerly anticipated.

Middle East respiratory syndrome (MERS-COV), first identified in Saudi Arabia, was caused by a novel strain of coronavirus. Outbreaks were recorded from different regions of the world, especially South Korea and the Middle East, and were correlated with a 35% mortality rate. MERS-COV is a single-stranded, positive RNA virus that reaches the host by binding to the receptor of dipeptidyl-peptides. Because of the unavailability of the vaccine available for the protection from MERS-COV infection, the rapid case detection, isolation, infection prevention has been recommended to combat MERS-COV infection. So, vaccines for the treatment of MERS-COV infection need to be developed urgently. A possible antiviral mechanism for preventing MERS-CoV infection has been considered to be MERS-CoV vaccines that elicit unique T-cell responses. In the present study, we incorporated both molecular docking and immunoinformatic approach to introduce a multiepitope vaccine (MEP) against MERS-CoV by selecting 15 conserved epitopes from seven viral proteins such as three structural proteins (envelope, membrane, and nucleoprotein) and four non-structural proteins (ORF1a, ORF8, ORF3, ORF4a). The epitopes, which were examined for non-homologous to host and antigenicity, were selected on the basis of conservation between T-cell, B-cell, and IFN-γ epitopes. The selected epitopes were then connected to the adjuvant (β-defensin) at the N-terminal through an AAY linker to increase the immunogenic potential. Structural modelling and physiochemical characteristic were applied to the vaccine construct developed. Afterwards the structure has been successfully docked with antigenic receptor, Toll-like receptor 3 (TLR-3) and in-silico cloning ensures that its expression efficiency is legitimate. Nonetheless the MEP presented needs tests to verify its safety and immunogenic profile.

Human T-cell lymphotropic virus type 1 (HTLV-1) is an infectious virus that has been linked to adult T cell leukemia /lymphoma, aggressive CD4-T cell malignancy and many other immune-related medical illnesses. So far, no effective vaccine is known to combat HTLV-1, hence, the current research work was performed to design a potential multi-epitope-based subunit vaccine (MEBV) by adopting the latest methodology of reverse vaccinology. Briefly, three highly antigenic proteins (Glycoprotein, Accessory protein, and Tax protein) with no or minimal (

BackgroundAlthough COVID-19 is an acute disease that usually resolves rapidly in most cases, the disease can be fatal and has a mortality rate of about 1% to 56%. Alveolar injury and respiratory failure are the main causes of death in patients with COVID 19. In addition, the effect of the disease on other organs is not fully understood. Renal system affection has been reported in patients with COVID 19 and is associated with a higher rate of diverse outcomes, including mortality. Therefore, in the present work, we reported the clinical characteristics and laboratory data of hospitalized patients with COVID-19 and analyzed the manifestations that indicated renal system involvement and their impact on clinical outcomes.Materials and methodsThis was an observational retrospective study conducted at King Fahd Specialist Hospital, Buraydah, Saudi Arabia. All patients with COVID-19 who were admitted to this Hospital from April to December 2020 were included in the study. The patients' findings at presentation were recorded. Demographic data and laboratory results (hematuria, proteinuria, urinary sediment cast and pus cell presence, and kidney function tests) were retrieved from electronic patient records.ResultsOne hundred and ninety-three patients with confirmed COVID 19 were included in the study. Dipstick examinations of all urine samples showed proteinuria and hematuria in 53.9% and 22.3% of patients, respectively, whereas microscopic examination revealed the presence of pus and brown muddy granular casts in 33.7% and 12.4% of samples, respectively. Acute kidney injury was reported in 23.3% of patients. A multivariable analysis demonstrated that hematuria was associated with acute kidney injury (AKI) (OR, 2.4; 95% CI, 1.2-4.9; P = 0.001), ICU admission (OR, 3.789; 95% CI, 1.913-7.505; P = 0.003), and mortality (OR, 8.084; 95% CI, 3.756-17.397; P = 0.002). Conversely, proteinuria was less significantly associated with the risk of AKI (OR, 1.56; 95% CI, 1.91-7.50; P = 0.003), ICU admission (OR, 2.493; 95% CI, 1.25-4.72; P = 0.001), and mortality (OR, 2.764; 95% CI, 1.368-5.121; P = 0.003). Patients with AKI had a higher probability for mortality than did those without AKI (OR, 14.208; 95% CI, 6.434-31.375; P = 0.003).ConclusionThe manifestations of the involvement of the renal system are not uncommon in COVID-19. These manifestations included proteinuria, hematuria, and AKI and were usually associated with a poor prognosis, including high incidences of both ICU admission and mortality.

BackgroundPrevalence of different respiratory allergies is increasing in the Kingdom of Saudi Arabia (KSA). Environmental risk factors of respiratory allergy vary regionally, hence the prevalence. This necessitates the needs for regional studies. This article reports prevalence and symptoms of respiratory allergies in the Qassim region, and the factors associated with the prevalence.MethodsEight hundred and fifty individuals aged ≥18 years and were living in the Qassim region filled up our structured online questionnaire between September and December 2020. We estimated the prevalence of different respiratory allergies with 95% confidence intervals. Multi-variable logistic regression analyses were performed to investigate the risk factors of respiratory allergies.FindingsThe prevalence of any respiratory allergy in the Qassim region was 28.8%. Most families (58.1%) had at least one member with respiratory allergy. The prevalence of allergic rhinitis and bronchial asthma were 13.5% and 11.2% 4.1% respectively. The reported symptoms included runny nose (13.6%), red, watery, and itchy eyes (10.4%), difficulty sleeping at night (10.2%), difficulty breathing in cold weather (9.2%), noisy breathing (8.5%), sneezing (8%), repeated coughing (7.5%) and shortness of breath (6.4%). Individuals with a family history were more likely to report any respiratory allergy (OR: 7.8), bronchial asthma (OR: 4.2) and allergic rhinitis (OR: 8.1) compared to the individuals without such family history. Odds of respiratory allergies was higher among males (OR: 1.5). Saudi nationals were less likely to report allergic rhinitis than the non-Saudis (OR: 0.4). Among those who reported a respiratory allergy, most (73.5%) received treatment and majority (61.7%) demonstrated compliance to the treatment, 8.8% needed hospitalization, and 23.1% needed emergency nebulization.ConclusionsPrevalence reported in our study is different than that reported in other regions. Variability in the environmental exposures might explain this. We recommend a meta-analysis to estimate the national prevalence of respiratory allergies.

Diethylnitrosamine (DEN) is a well-known hepatocarcinogen, and its oral administration causes severe liver damage including cancer. DEN induces the pathogenesis of the liver through reactive oxygen species mediated inflammation and modulation of various biological activities. 6-Gingerol, a major component of ginger, is reported to prevent liver diseases by reducing the oxidative stress and proinflammatory mediators. The present study investigated the hepatoprotective effects of 6-gingerol through the measurement of oxidative stress, anti-inflammatory markers, liver function enzyme parameter, and histopathological analysis. The rats were randomly divided into four groups as the control, DEN treated (50 mg/kg b.w.), DEN+6-gingerol (each 50 mg/kg b.w.), and 6-gingerol only. To evaluate the hepatoprotective effects, liver function enzymes (ALT, AST, and ALP), oxidative stress markers (SOD, GSH, GST, and TAC), lipid peroxidation, inflammatory markers (CRP, TNF-α, IL-6, and ICAM1), haematoxylin and eosin staining, Sirius red staining, immunohistochemistry, and electron microscopy were performed. The results showed a significant increase in liver function enzymes, oxidative stress, and inflammatory markers in the DEN-treated group as compared to the control group. Besides this, altered architecture of hepatocytes (infiltration of inflammatory cells, congestion, blood vessel dilation, and edema), abundant collagen fiber and organelle structures like distorted shaped and swollen mitochondria, and broken endoplasmic reticulum were noticed. The administration of 6-gingerol significantly ameliorated the biochemical and histopathological changes. The increased expression of TNF-α protein was noticed in the DEN-treated group whereas the administration of 6-gingerol significantly decreased the expression of this protein. Based on these findings, it can be suggested that 6-gingerol may be an alternative therapy for the prevention and treatment of liver diseases.

Background. The term “persisters” refers to a small bacterial population that persists during treatment with high antibiotic concentration or dose in the absence of genetic resistance. The present study was designed to investigate the transcriptional response in indigenous Klebsiella pneumoniae under the ciprofloxacin stress. Methods. Isolation and identification of K. pneumoniae were carried out through standard microbiological protocols. The characterization of quinolone resistance was performed by estimating the quinolone susceptibility testing, MIC estimation, and detecting the QRDR and PMQR. Transcriptional response of the isolates to ciprofloxacin was determined using qPCR. Results. Among 34 isolates, 23 (67%) were resistant to ciprofloxacin. Both QRDR (gyrA and gyrB) and PMQR (qnrA, qnrB, and qnrS) were detected in the isolates, and all were found resistant to ciprofloxacin. The mRNA levels of both mutS and euTu under the influence of ciprofloxacin were significantly increased. On ciprofloxacin exposure, the mRNA levels of the DNA damage response element (mutS) were raised in a time-dependent fashion. K. pneumoniae showed high-level resistance to ciprofloxacin in the presence of mutations in QRDR and PMQR genes. Conclusion. The transcriptional response revealed the upregulation of DNA repair and protein folding elements (mutS and euTu) in ciprofloxacin stress and delayed cell division. The ciprofloxacin was found to trigger various stress responses in a time- and concentration-dependent manner.

The present study aimed at investigating the 4G/5G and -844G/A polymorphisms and plasma concentration of PAI-1 in patients with acute myocardial infarction (AMI) and chronic stable angina (CSA) in Indian population. It included 100 patients with AMI and stable angina and 100 healthy controls. All study subjects were typed for two PAI polymorphisms (4G/5G and -844G/A) through PCR-RFLP and level of PAI through ELISA. The comparison of AMI and CSA independently with control in terms of PAI-1 level was statistically significant but not between AMI and CSA. The frequency of 4G/4G and 4G/5G genotype and 4G allele was significantly higher in AMI cases than in control and was found to increase the risk of AMI. There was a significant relationship between 4G/5G polymorphism and AMI risk under the dominant and codominant genotype. The frequency of 4G/4G genotype and 4G allele was significantly higher in CSA cases than in control group and increases the risk of CSA. There was no significant association between 4G/5G polymorphism and CSA risk under recessive, dominant, and codominant models. The genotype and allelic frequencies difference between the cases (AMI and CSA) and control with regard to -844G/A polymorphisms were statistically nonsignificant. Also, we did not detect any significant association of -844G/A polymorphism with AMI and CSA in recessive, dominant, and codominant models. Along with the traditional risk factors, the 4G/5G allele polymorphism is an independent risk factor for the development of AMI. The detection of 4G/5G allele may therefore be helpful in primary prevention. Patients who carry the 4G/5G allele polymorphism have high concentrations of PAI-1, which might be involved in incidents leading to AMI. The present study for the first time revealed significant association of 4G/5G allele polymorphism with high risk of AMI in Indian population and will be helpful in identifying the genetic risk factors associated with AMI and CSA and for better management of diagnostic measures.

Hyperactivation of the host immune system during infection by SARS-CoV-2 is the leading cause of death in COVID-19 patients. It is also evident that patients who develop mild/moderate symptoms and successfully recover display functional and well-regulated immune response. Whereas a delayed initial interferon response is associated with severe disease outcome and can be the tipping point towards immunopathological deterioration, often preceding death in COVID-19 patients. Further, adaptive immune response during COVID-19 is heterogeneous and poorly understood. At the same time, some studies suggest activated T and B cell response in severe and critically ill patients and the presence of SARS-CoV2-specific antibodies. Thus, understanding this problem and the underlying molecular pathways implicated in host immune function/dysfunction is imperative to devise effective therapeutic interventions. In this comprehensive review, we discuss the emerging immunopathological determinants and the mechanism of virus evasion by the host cell immune system. Using the knowledge gained from previous respiratory viruses and the emerging clinical and molecular findings on SARS-CoV-2, we have tried to provide a holistic understanding of the host innate and adaptive immune response that may determine disease outcome. Considering the critical role of the adaptive immune system during the viral clearance, we have presented the molecular insights of the plausible mechanisms involved in impaired T cell function/dysfunction during various stages of COVID-19.

Acute lung injury (ALI) is a well-known respiratory disease and a leading cause of death worldwide. Despite advancements in the medical field, developing complete treatment strategies against this disease is still a challenge. In the current study, the therapeutic role of prostaglandin D2 (PGD2) was investigated on lipopolysaccharide (LPS)-induced lung injury in mice models and RAW264.7 macrophages through anti-inflammatory, histopathology, immunohistochemistry, and TUNEL staining. The overproduction of cytokines by RAW264.7 macrophages was observed after stimulation with LPS. However, pretreatment with PGD2 decreased the production of cytokines. The level of inflammatory markers was significantly restored in the PGD2 treatment group (TNF-α = 58.6 vs. 78.5 pg/mL; IL-1β = 29.3 vs. 36.6 pg/mL; IL-6 = 75.4 vs. 98.2 pg/mL; and CRP = 0.84 vs. 1.14 ng/mL). The wet/dry weight ratio of the lungs was quite significant in the disease control (LPS-only treatment) group. Moreover, the histological changes as determined by haematoxylin and eosin (H&E) staining clearly showed that PGD2 treatment maintains the lung tissue architecture. The iNOS expression pattern was increased in lung tissues of LPS-treated animals, whereas, in mice treated with PGD2, the expression of iNOS protein decreased. Flow cytometry data demonstrated that LPS intoxication enhanced apoptosis, which significantly decreased with PGD2 treatment. In conclusion, all these observations indicate that PGD2 provides an anti-inflammatory response in RAW264.7 macrophages and in ALI, and they suggest a therapeutic potential in lung pathogenesis.

Enterobacter cloacae (EC) is a significant emerging pathogen that is occasionally associated with lung infection, surgical site infection, urinary infection, sepsis, and outbreaks in neonatal intensive care units. In light of the fact that there is currently no approved vaccine or therapeutic option for the treatment of EC, the current study was developed to concentrate on applications based on modern computational approaches to design a multi-epitope-based E. cloacae peptide vaccine (MEBEPV) expressing the antigenic determinants prioritized from the EC genome. Integrated computational analyses identified two potential protein targets (phosphoporin protein-PhoE and putative outer-membrane porin protein) for further exploration on the basis of pangenome subtractive proteomics and immunoinformatic in-depth examination of the core proteomes. Then, a multi-epitope peptide vaccine was designed, which comprised shortlisted epitopes that were capable of eliciting both innate and adaptive immunity, as well as the cholera toxin’s B-subunit, which was used as an adjuvant in the vaccine formulation. To ensure maximum expression, the vaccine’s 3D structure was developed and the loop was refined, improving the stability by disulfide engineering, and the physicochemical characteristics of the recombinant vaccine sequence were found to be ideal for both in vitro and in vivo experimentation. Blind docking was then used for the prediction of the MEBEPV predominant blinding mode with MHCI, MHCII, and TLR3 innate immune receptors, with lowest global energy of −18.64 kJ/mol, −48.25 kJ/mol, and −5.20 kJ/mol for MHC-I, MHC-II, and TLR-4, respectively, with docked complexes considered for simulation. In MD and MMGBSA investigations, the docked models of MEBEPV-TLR3, MEBEPV-MHCI, and MEBEPV-MHCII were found to be stable during the course of the simulation. MM-GBSA analysis calculated −122.17 total net binding free energies for the TLR3-vaccine complex, −125.4 for the MHC I-vaccine complex, and −187.94 for the MHC II-vaccine complex. Next, MM-PBSA analysis calculated −115.63 binding free energy for the TLR3-vaccine complex, −118.19 for the MHC I-vaccine complex, and −184.61 for the MHC II-vaccine complex. When the vaccine was tested in silico, researchers discovered that it was capable of inducing both types of immune responses (cell mediated and humoral) at the same time. Even though the suggested MEBEPV has the potential to be a powerful contender against E. cloacae-associated illnesses, further testing in the laboratory will be required before it can be declared safe and immunogenic.

Honey is the principal premier product of beekeeping familiar to Homo for centuries. In every geological era and culture, evidence can be traced to the potential usefulness of honey in several ailments. With the advent of recent scientific approaches, honey has been proclaimed as a potent complementary and alternative medicine for the management and treatment of several maladies including various neurological disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and multiple sclerosis, etc. In the literature archive, oxidative stress and the deprivation of antioxidants are believed to be the paramount cause of many of these neuropathies. Since different types of honey are abundant with certain antioxidants, primarily in the form of diverse polyphenols, honey is undoubtedly a strong pharmaceutic candidate against multiple neurological diseases. In this review, we have indexed and comprehended the involved mechanisms of various constituent polyphenols including different phenolic acids, flavonoids, and other phytochemicals that manifest multiple antioxidant effects in various neurological disorders. All these mechanistic interpretations of the nutritious components of honey explain and justify the potential recommendation of sweet nectar in ameliorating the burden of neurological disorders that have significantly increased across the world in the last few decades.

Rift valley fever virus (RVFV) is the causative agent of a viral zoonosis that causes a significant clinical burden in domestic and wild ruminants. Major outbreaks of the virus occur in livestock, and contaminated animal products or arthropod vectors can transmit the virus to humans. The viral RNA-dependent RNA polymerase (RdRp; L protein) of the RVFV is responsible for viral replication and is thus an appealing drug target because no effective and specific vaccine against this virus is available. The current study reported the structural elucidation of the RVFV-L protein by in-depth homology modeling since no crystal structure is available yet. The inhibitory binding modes of known potent L protein inhibitors were analyzed. Based on the results, further molecular docking-based virtual screening of Selleckchem Nucleoside Analogue Library (156 compounds) was performed to find potential new inhibitors against the RVFV L protein. ADME (Absorption, Distribution, Metabolism, and Excretion) and toxicity analysis of these compounds was also performed. Besides, the binding mechanism and stability of identified compounds were confirmed by a 50 ns molecular dynamic (MD) simulation followed by MM/PBSA binding free energy calculations. Homology modeling determined a stable multi-domain structure of L protein. An analysis of known L protein inhibitors, including Monensin, Mycophenolic acid, and Ribavirin, provide insights into the binding mechanism and reveals key residues of the L protein binding pocket. The screening results revealed that the top three compounds, A-317491, Khasianine, and VER155008, exhibited a high affinity at the L protein binding pocket. ADME analysis revealed good pharmacodynamics and pharmacokinetic profiles of these compounds. Furthermore, MD simulation and binding free energy analysis endorsed the binding stability of potential compounds with L protein. In a nutshell, the present study determined potential compounds that may aid in the rational design of novel inhibitors of the RVFV L protein as anti-RVFV drugs.

Green nanotechnology is the evolution of cost-effective and environmentally friendly processes for the production of metal-based nanoparticles due to medicinal importance and economic value. The aim of the present study was to biosynthesize and characterize silver nanoparticles (AgNPs) using the seed extract of Ajwa dates (Aw). The anti-bacteriostatic activity of biosynthesized Aw–AgNPs against Gram-positive and Gram-negative bacterial strains was evaluated. The anti-biofilm activity was examined by the tissue culture plate method. Lastly, the anti-cancer potential of Aw–AgNPs was investigated against the human breast cancer cell line HCC712. UV–visible absorption spectra exhibited the plasmon resonance peak at 430 nm, with the solution undergoing rapid color changes that verified the existence of biosynthesized silver nanoparticles in the solution. TEM and SEM images illustrated that the Aw–AgNPs were spherical and between 15 and 80 nm in diameter. The reduction and stabilization of Aw–AgNPs was due to the functional groups present in the biomolecules of the Ajwa seeds, as identified by FTIR. The Aw–AgNPs exhibited significant anti-bacterial activity against all the tested bacterial strains. Moreover, the Aw–AgNPs efficiently hampered the biofilm formation of the bacterial strains and exhibited cytotoxicity at various concentrations. Overall, these findings suggest that biosynthesized Aw–AgNPs may be used as a potential therapeutic formulation against bacterial infections and breast cancer.

Due to the misuse of antibiotics in our daily lives, antimicrobial resistance (AMR) has become a major health problem. Penicillin, the first antibiotic, was used in the 1930s and led to the emergence of AMR. Due to alterations in the microbe’s genome and the evolution of new resistance mechanisms, antibiotics are losing efficacy against microbes. There are high rates of mortality and morbidity due to antibiotic resistance, so addressing this major health issue requires new approaches. Staphylococcus auricularis is a Gram-positive cocci and is capable of causing opportunistic infections and sepsis. S. auricularis is resistant to several antibiotics and does not currently have a licensed vaccine. In this study, we used bacterial pan-genome analysis (BPGA) to study S. auricularis pan-genome and applied a reverse immunology approach to prioritize vaccine targets against S. auricularis. A total of 15,444 core proteins were identified by BPGA analysis, which were then used to identify good vaccine candidates considering potential vaccine filters. Two vaccine candidates were evaluated for epitope prediction including the superoxide dismutase and gamma-glutamyl transferase protein. The epitope prediction phase involved the prediction of a variety of B-Cell and T-cell epitopes, and the epitopes that met certain criteria, such as antigenicity, immunogenicity, non-allergenicity, and non-toxicity were chosen. A multi-epitopes vaccine construct was then constructed from all the predicted epitopes, and a cholera toxin B-subunit adjuvant was also added to increase vaccine antigenicity. Three-dimensional models of the vaccine were used for downward analyses. Using the best-modeled structure, binding potency was tested with MHC-I, MHC-II and TLR-4 immune cells receptors, proving that the vaccine binds strongly with the receptors. Further, molecular dynamics simulations interpreted strong intermolecular binding between the vaccine and receptors and confirmed the vaccine epitopes exposed to the host immune system. The results support that the vaccine candidate may be capable of eliciting a protective immune response against S. auricularis and may be a promising candidate for experimental in vitro and in vivo studies.

Gorgostane steroids are isolated from marine organisms and consist of 30 carbon atoms with a characteristic cyclopropane moiety. From the pioneering results to the end of 2021, isolation, biosynthesis, and structural elucidation using 13C-NMR will be used. Overall, 75 compounds are categorized into five major groups: gorgost-5-ene, 5,6-epoxygorgostane, 5,6-dihydroxygorgostane, 9,11-secogorgostane, and 23-demethylgorgostane, in addition to miscellaneous gorgostane. The structural diversity, selectivity for marine organisms, and biological effects of gorgostane steroids have generated considerable interest in the field of drug discovery research.

This study investigated the health-promoting activities of methanolic extracts of Ajwa date seed and fruit pulp extracts through in vitro studies. These studies confirmed potential antioxidant, anti-hemolytic, anti-proteolytic, and anti-bacterial activities associated with Ajwa dates. The EC50 values of fruit pulp and seed extracts in methanol were reported to be 1580.35 ± 0.37 and 1272.68 ± 0.27 µg/mL, respectively, in the DPPH test. The maximum percentage of hydrogen peroxide-reducing activity was 71.3 and 65.38% for both extracts at 600 µg/mL. Fruit pulp and seed extracts inhibited heat-induced BSA denaturation by 68.11 and 60.308%, heat-induced hemolysis by 63.84% and 58.10%, and hypersalinity-induced hemolysis by 61.71% and 57.27%, and showed the maximum anti-proteinase potential of 56.8 and 51.31% at 600 μg/mL, respectively. Seed and fruit pulp inhibited heat-induced egg albumin denaturation at the same concentration by 44.31 and 50.84%, respectively. Ajwa seed showed minimum browning intensity by 63.2%, percent aggregation index by 64.2%, and amyloid structure by 63.8% at 600 μg/mL. At 100 mg/mL, Ajwa seed extract exhibited good antibacterial activity. Molecular docking analysis showed that ten active constituents of Ajwa seeds bind with the critical antioxidant enzymes, catalase (1DGH) and superoxide dismutase (5YTU). The functional residues involved in such interactions include Arg72, Ala357, and Leu144 in 1DGH, and Gly37, Pro13, and Asp11 in 5YTU. Hence, Ajwa dates can be used to develop a suitable alternative therapy in various diseases, including diabetes and possibly COVID-19-associated complications.